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Anti-Proliferative and Apoptotic Activities of M?llerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines.

 Yeon Soo Jung  ;  Hee Jung Kim  ;  Seok Kyo Seo  ;  Young Sik Choi  ;  Eun Ji Nam  ;  Sunghoon Kim  ;  Sang Wun Kim  ;  Hyuck Dong Han  ;  Jae Wook Kim  ;  Young Tae Kim 
 YONSEI MEDICAL JOURNAL, Vol.57(1) : 33-40, 2016 
Journal Title
Issue Date
Anti-Mullerian Hormone/pharmacology* ; Apoptosis/drug effects* ; Calcitriol/pharmacology* ; Caspase 3/metabolism ; Caspase 9/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Cell Survival/drug effects ; DNA Fragmentation/drug effects* ; Enzyme-Linked Immunosorbent Assay ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Growth Inhibitors/metabolism ; Growth Inhibitors/pharmacology ; Humans ; Ovarian Neoplasms/drug therapy* ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology* ; Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; Signal Transduction/drug effects*
Müllerian inhibiting substance ; Ovarian cancer ; antiproliferation ; apoptosis ; calcitriol
PURPOSE: This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis.
MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway.
RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway.
CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Sung Hoon(김성훈) ORCID logo https://orcid.org/0000-0002-1645-7473
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Nam, Eun Ji(남은지) ORCID logo https://orcid.org/0000-0003-0189-3560
Seo, Seok Kyo(서석교) ORCID logo https://orcid.org/0000-0003-3404-0484
Choi, Young Sik(최영식) ORCID logo https://orcid.org/0000-0002-1157-4822
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